【摘 要】
：
Human ACAT2 is mainly expressed in intestine and fetal liver.Our previous studies have demonstrated that the high-level expression of human ACAT2 gene with the CpG hypomethylation of its whole promote
【机 构】
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State Key Laboratory of Molecular Biology,Institute of Biochemistry and Cell Biology,Shanghai Instit
【出 处】
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中国生物化学与分子生物学会2016年全国学术会议
论文部分内容阅读
Human ACAT2 is mainly expressed in intestine and fetal liver.Our previous studies have demonstrated that the high-level expression of human ACAT2 gene with the CpG hypomethylation of its whole promoter is synergistically regulated by two transcription factors Cdx2 and HNF1α in the intestine and also in certain hepatocellular carcinoma(HCC)tissues.Here,we report that the low-level expression of human ACAT2 gene in THP-1 cells is correlated with its specific CpG-hypomethylated promoter,and regulated by C/EBP transcription factors.Consistently,the expressions of ACAT2 and C/EBPs are increased in macrophages differentiated from both ATRA-treated THP-1 cells and cultured human blood monocytes.Then,we further find that in all human leukocytes,the low-level expression of ACAT2 gene is not only attributed to the C/EBPs but also correlated with the excretion of fluorescent lipoproteins containing the ACAT2-catalyzed NBD22-steryl esters.Moreover,this lipoprotein excretion can be inhibited by the ACAT2 isoform-selective inhibitor PPPA in a dose-dependent manner,and employed to determine the half maximum inhibitory concentration(IC50)values of PPPA.More importantly,our results show that the differentiation-inducing factor all-trans retinoic acid(ATRA),but not the proinflammatory cytokine tumor necrosis factor-α(TNF-α),enhances this ACAT2-dependent lipoprotein excretion.These data demonstrate that in human leukocytes,ACAT2 is responsible for the excretion of lipoproteins containing cholesteryl/steryl esters,and indicate that the excretion of lipoproteins containing the ACAT2-catalyzed cholesteryl/steryl esters may avoid cytotoxicity through decreasing the excess intracellular cholesterols/sterols(especially various oxysterols),which is essential for the action of the human leukocytes.
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